Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation.
Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34(+) cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity.
Bousquet
Marina
M
Institut National de Santé et de Recherche Médicale, U563, Centre de Physiopathologie de Toulouse-Purpan, 31300 Toulouse, France.
Quelen
Cathy
C
Rosati
Roberto
R
Mansat-De Mas
Véronique
V
La Starza
Roberta
R
Bastard
Christian
C
Lippert
Eric
E
Talmant
Pascaline
P
Lafage-Pochitaloff
Marina
M
Leroux
Dominique
D
Gervais
Carine
C
Viguié
Franck
F
Lai
Jean-Luc
JL
Terre
Christine
C
Beverlo
Berna
B
Sambani
Costantina
C
Hagemeijer
Anne
A
Marynen
Peter
P
Delsol
Georges
G
Dastugue
Nicole
N
Mecucci
Cristina
C
Brousset
Pierre
P
D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D022423:Myeloid Cells / Q000166:cytology* / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
D017931:DNA Primers; C531888:MIRN125 microRNA, human; D035683:MicroRNAs